This project will study the behavior of purified human mesenchymal stem cells (MSC) after in utero transplantation. These non- hematopoetic bone marrow stem cells serve as precursors for a variety of tissues, including bone, cartilage, muscle, tendon, and bone marrow stroma. We will first examine the homing and differentiation patterns of human MSC in the fetal lamb recipient. We will then transduce MSC with a retroviral vector expressing lacZ to explore their potential for in utero gene therapy. The rationale for prenatal transplantation is to take advantage of the "window of opportunity" in fetal development, prior to the population of bone marrow and thymic processing of self-antigen, when the fetus is receptive to engraftment of foreign cells without rejection or the need for myeloablation. Such treatments could preempt postnatal complications of many congenital diseases. If MSC are found to engraft in a host, distribute widely, and differentiate into various cell types, they could be used to correct metabolic or structural defects such as muscular dystrophy or osteogenesis imperfecta. Co-transplantation of MSC with hematopoetic cells would also improve engraftment in treating immunodeficiency disorders. Finally, if virally transduced MSC can engraft in a host and express a gene of interest, they could be used for systemic delivery of hormones, clotting factors enzymes, or growth factors.